Suppression of dopamine-related side effects of morphine by aripiprazole, a dopamine system stabilizer.
Dopamine receptor antagonists are commonly used to counter the adverse effects of opioids such as hallucinations, delusions and emesis. However, most of these agents themselves have side effects, including extrapyramidal symptoms. Here, we investigated the effect of the dopamine system stabilizer aripiprazole on morphine-induced dopamine-related actions in mice. Morphine-induced hyperlocomotion and reward were significantly suppressed by either the dopamine receptor antagonist prochlorperazine or aripiprazole. Catalepsy was observed with a high dose of prochlorperazine, but not with an even higher dose of aripiprazole. The increased level of dialysate dopamine in the nucleus accumbens stimulated by morphine was significantly decreased by pretreatment with aripiprazole. These results suggest that the co-administration of aripiprazole may be useful for reducing the severity of morphine-induced dopamine-related side effects.
Narita
Minoru
M
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. narita@hoshi.ac.jp
Takei
Daisuke
D
Shiokawa
Mitsuru
M
Tsurukawa
Yuri
Y
Matsushima
Yuki
Y
Nakamura
Atsushi
A
Takagi
Shigemi
S
Asato
Megumi
M
Ikegami
Daigo
D
Narita
Michiko
M
Amano
Taku
T
Niikura
Keiichi
K
Hashimoto
Keisuke
K
Kuzumaki
Naoko
N
Suzuki
Tsutomu
T
D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068180:Aripiprazole; D002375:Catalepsy / Q000139:chemically induced; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000009:adverse effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011346:Prochlorperazine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012201:Reward; D012720:Severity of Illness Index
D000701:Analgesics, Opioid; D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D010879:Piperazines; D015363:Quinolones; D009020:Morphine; D000068180:Aripiprazole; D004298:Dopamine; D011346:Prochlorperazine